This is a bug introduced in 12.0.7 and persists into 12.1 with no resolution/fix.
Currently (and for the last two months) if you hold down any of the standard modifier keys (like control) while clicking a frame you are unable to select that frame. This has never been a limitation in the game. Naturally it has made frame interaction (healing) a nightmare. Especially as someone who uses ctrl for push to talk while playing.
It is suspected that click to cast changes introduced in 12.0.7 broke basic modifier function. Some community fixes have been to go in and reset click to cast settings to defaults. This isnt a fix unless you were someone already using click to cast (which isnt the subject of this bug report). Other solutions have been to manually make target marcros for EVERY SINGLE ABILITY/FUNCTION. Also no a fix.
A basic search below shows the multitude of threads on this with no Blizzard response (that I can find).
Bumping this as it’s not being publicly tracked as a bug (doubt it ever will be).
For anyone who needs a band-aid solution checkout the addon “Shift Click Target Fix”
Shouldn’t have to use an addon (which now introduces some level of resource overhead) to fix something that has been busted this long. But this is where we are.
Bump - this functionality was suddenly changed after working a certain way since the original game came out. It does not seem intentional. Blizzard please fix!